Inhibitor of DNA binding-1 is a key regulator of cancer cell vasculogenic mimicry

  • Mol Oncol. 2025 Mar 21. doi: 10.1002/1878-0261.70027.
Emma J Thompson  1 ,  Emma L Dorward  1 ,  Kristyn Jurrius  1 ,  Nathalie Nataren  1 ,  Markus Tondl  1 ,  Kay K Myo Min  1 ,  Michaelia P Cockshell  1 ,  Anahita Fouladzadeh  1 ,  John Toubia  1  2 ,  Mark DeNichilo  1 ,  Delphine Merino  3  4  5  6 ,  Claudine S Bonder  1  7
Affiliations
  • 1. Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia.
  • 2. ACRF Cancer Genomics Facility, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia.
  • 3. Olivia Newton John Cancer Research Institute, Melbourne, Australia.
  • 4. School of Cancer Medicine, La Trobe University, Bundoora, Australia.
  • 5. Department of Medical Biology, The Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
  • 6. Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • 7. Adelaide Medical School, University of Adelaide, Australia.
PMID: 40116596 DOI: 10.1002/1878-0261.70027
Abstract

Solid tumours routinely access the blood supply by promoting endothelium-dependent angiogenesis; but tumour vasculature can also be formed by Cancer cells themselves via vasculogenic mimicry (VM). Investigation of the gene expression profile during the early stages of VM formation by MDA-MB-231-LM2 breast Cancer cells identified the transcriptional regulator inhibitor of DNA binding 1 (ID1) to be elevated ~ 10-fold within the first 2 hours. This role for ID1 in promoting VM was supported by ID1 genetic knockdown or chemical inhibition interrupting VM formation by MDA-MB-231-LM2 (breast) and BxPC-3 (pancreatic) Cancer cells. More specifically, reducing ID1 lowered Cancer cell expression of endothelial cell genes (e.g. CDH5, Tie2) and production of pro-angiogenic proteins (e.g. VEGF, CD31, MMP9 and IL-8). In silico analysis of MDA-MB-231 cells engrafted into mice identified elevated ID1 expression in Cancer cells that had metastasised to the lungs or liver, and an enrichment of pro-angiogenic genes. Additionally, Id1 knockdown in 4T1.13 murine breast Cancer cells demonstrated reduced tumour growth and metastasis in vivo. Taken together, this study further implicates ID1 in a vascular program within Cancer cells that supports disease progression.

Keywords
ID1; breast cancer; pancreatic cancer; tumour vasculature; vasculogenic mimicry.
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